title: Permanent activation of HMGA2 in lipomas mimics its temporal physiological activation linked to the gain of adipose tissue.
abstract: OBJECTIVE
  In this study the activation of HMGA2 and overexpression by FGF1-driven stimulation of adipose tissue derived stem cells (ADSCs) in adipose tissue tumors were analyzed. In addition, the expression of HMGA2 and PPAR-gamma mRNA were quantified in canine subcutaneous abdominal adipose tissue from normal and overweight purebred dogs.
  
  
  METHODS
  ADSCs and adipose tissue explants stimulated with FGF1 followed by gene expression analyses of HMGA2 and p14(Arf) using Western-blot and qRT-PCR. Furthermore, canine subcutaneous white adipose tissue (WAT) were analyzed by qRT-PCR for their expression of HMGA2 and PPAR-gamma.
  
  
  RESULTS
  ADSCs and adipose tissue explants are able to execute a HMGA2 response upon FGF1 stimulation. FGF1 enhances proliferation of ADSCs by a HMGA2-dependent mechanism. In lipomas increase of HMGA2 is accompanied by increased expression of p14(Arf) . Furthermore, a significantly elevated level of HMGA2 in overweight dogs and a negative correlation between the expression of HMGA2 and PPAR-gamma in subcutaneous cWAT were noted.
  
  
  CONCLUSIONS
  These results suggest that WAT contains cells that as essential part of adipogenesis up-regulate HMGA2 resulting from growth factor stimulation. In subgroups of lipoma, constitutive activation of HMGA2 due to rearrangements replaces the temporal response triggered by growth factors.
authors.affiliation: Center of Human Genetics, University of Bremen, Leobener Strasse ZHG, D-28359 Bremen, Germany.
authors.forename: Helge W
authors.initials: HW
authors.lastname: Thies
authors.forename: Ingo
authors.initials: I
authors.lastname: Nolte
authors.forename: Heiner
authors.initials: H
authors.lastname: Wenk
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
authors.forename: Jörn
authors.initials: J
authors.lastname: Bullerdiek
authors.forename: Dominique N
authors.initials: DN
authors.lastname: Markowski
mesh_terms: D050156:Adipogenesis / Q000235:genetics / Q000502:physiology; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D015321:Gene Rearrangement; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008067:Lipoma / Q000378:metabolism*; D008297:Male; D050177:Overweight / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D050507:Subcutaneous Fat, Abdominal / Q000166:cytology*; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D025743:HMGA2 Protein; D047495:PPAR gamma; D012333:RNA, Messenger; D025803:Tumor Suppressor Protein p14ARF; D016220:Fibroblast Growth Factor 1